There is a great deal of controversy about the potential effects of food flavonoids on cardiovascular disease risk. This is, in part, a consequence of the absence, until recently, of a complete food flavonoid database and the potential for differential effects of the various classes of flavonoids. Some epidemiological evidence of cardiovascular disease risk reduction is available for the flavanol class (including catechins and flavanones). Epidemiological evidence is available, though variable, for the flavone, flavonol and isoflavone classes whereas associations between the anthocyanins and cardiovascular risk have not been investigated. The goal of the present study is to further our understanding of the role of dietary flavonoids in cardiovascular disease by examining the relation between intake of the different flavonoid classes and various intermediate markers of cardiovascular disease. Specifically, we will examine the associations between five classes of dietary flavonoids (flavanols, anthocyanins, flavones, flavonols, and isoflavones) and the following CVD risk factors: inflammatory markers including C-reactive protein, interleukin 6, monocyte chemoattractant protein-1, and tumor necrosis factor alpha; fibrinolytic factors including fibrinogen and P-selectin; lipids including high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, and triglycerides; endothelial function by assessed by flow mediated dilation (brachial artery reactivity); and blood pressure. Our hypothesis is that a higher intake of the flavanol class of flavonoids (which includes the catechins, proanthocyanidins, and flavanones) is associated with a healthier profile of intermediate markers of cardiovascular disease risk. In contrast to the flavanols, intakes of other classes of flavonoids (anthocyanins, flavones, flavonols, and isoflavonoids) are not expected to be as strongly associated with lower CVD risk as indicated by intermediate biomarkers. We plan to examine this hypothesis using previously collected and measured data from the seventh examination of Framingham Heart Study Offspring Cohort. Working with the Framingham investigators, we will link an enhanced and updated flavonoid database to dietary information collected with a food frequency questionnaire. Amounts of each food flavonoid will be entered in a database for each item on the questionnaire. The extended database will allow more complete assessment of flavonoid intakes than has previously been possible. It should be noted that the study investigators have extensive experience with addition of flavonoids to other food frequency questionnaires, and therefore we anticipate no problems in accomplishing this. The proposed project presents an efficient and effective means to examine the potential relationship between flavonoids and cardiovascular disease risk. There is evidence that foods high in certain flavonoids are associated with better metabolic risk factors for cardiovascular disease, but almost all of the human evidence relating flavonoids to cardiovascular disease risk is based on studies of flavonoid-containing foods, not flavonoid intake. Consequently, this evidence may be confounded by other components of flavonoid-rich foods. This proposed research should help to clarify the controversy and confusion about the influence of flavonoids on cardiovascular disease risk by examining the relation between dietary intake of specific flavonoids and metabolic risk factors for cardiovascular disease. [unreadable] [unreadable] [unreadable]